Study included 3 treatment groups and a placebo group: 50 mg ABT-450 / 100 mg Ritonavir, 100 mg ABT-450 / 100 mg Ritonavir, 200 mg ABT-450 / 100 mg Ritonavir; pts received treatment with ABT-450/Ritonavir once-daily for 3 days (monotherapy phase), followed at the end of the 3 days by combined treatment with ABT-450/Ritonavir and PEG-IFN alfa-2a 180 µg weekly plus Ribavirin 1000-1200 mg once daily based on pt's weight up to week 12, followed after week 12 by standard treatment only with PEG-IFN/Ribavirin through week 48

Profound decreases in HCV RNA levels were seen at all ABT-450/Ritonavir doses (similar for all doses): mean maximum decrease from baseline was 4.02 log10 IU/mL vs. 0.36 log10 for placebo group (p<0.001)

No treatment-related SAEs were reported

AEs included dizziness, headache and somnolence, and were generally mild

Results of the first 4 weeks of combined therapy with ABT-450/Ritonavir and PEG-IFN/Ribavirin were presented at 61st Annual Meeting of AASLD, Oct. 29-Nov. 2, 2010 by Lawitz et al., Poster LB10:

No additional relapses were seen among the 10 pts with 48-week post-
treatment data available / where SVR48 results were available

Most common AEs were headache (36%), fatigue (27%), nausea (27%) and dry skin (27%), most of which were mild in severity

Two bilirubin elevations, which consisted of indirect bilirubin with no
associated transaminase elevations, were reported during the study; they occurred one week after starting treatment and resolved with continued dosing

Results of an open-label Phase II pilot study (NCT01306617) evaluating a combination of ABT-450 (boosted with Ritonavir, ABT-450/r) with ABT-333 and Ribavirin were presented by Poordad et al. at the 47th Annual Meeting of the EASL, Apr. 18–22, 2012, Barcelona, Spain (Abstract 1399):

Sapphire-1 study was a multicenter, randomized, double-blind, placebo-controlled trial, in which previously untreated pts infected with HCV genotype 1 infection, with no cirrhosis, were assigned in a 3:1 ratio, to receive during a 12-week double-blind period a regimen consisting of single-tablet coformulation of ABT-450/r (ABT-450 150 mg boosted with 100 mg Ritonavir)–Ombitasvir (25 mg) once-daily, along with Dasabuvir (250 mg BID) and Ribavirin (dosed according to body weight) (group A), or matching placebos (group B)

A total of 631 pts received at least one dose of study drugs

Rate of sustained virologic response at 12 weeks after end of treatment (SVR12) in group A was 96.2% (95% confidence interval, 94.5 to 97.9), which was superior to historical control rate (78%) for previously untreated pts without cirrhosis who received Telaprevir with PEG-IFN and Ribavirin

Virologic failure during treatment and relapse after treatment occurred in 0.2% and 1.5%, respectively, of pts in group A

Response rates in group A were 95.3% among pts with HCV genotype 1a infection and 98.0% among those with HCV genotype 1b infection

Rate of discontinuation due to AEs was 0.6% in each study group

Nausea, pruritus, insomnia, diarrhea, and asthenia occurred in significantly more pts in group A than in group B (P<0.05 for all comparisons)

Reductions in the hemoglobin level were all of grade 1 or 2: reductions of grade 1 and 2 occurred in 47.5% and 5.8%, respectively, of pts in group A, whereas grade 1 reductions occurred in 2.5% of pts in group B

Development status

MarketApproved for market in US (Dec. 2014)and other markets as part of combination therapy called Viekira Pak;
See Remarks

Remarks

NS3/4A HCV serine protease inhibitors;

Abbott's antiviral program is focused on HCV;

Phase II studies consisted in evaluation of ABT-450 combined with other cpnds from sponsor, together with/without PEG-IFN/Ribavirin in HCV-infected treatment-naive or experienced pts;

On May 6, 2013, AbbVie announced that its investigational direct-acting antiviral (DAA) combination ABT-450/Ritonavir + ABT-267 + ABT-333 with and without Ribavirin, has been designated as Breakthrough Therapy by FDA for treatment of genotype 1 (GT1) HCV infection;

NDA was filed by AbbVie to FDA in Apr. 2014 for US market, for combination therapy consisting of ABT-267 (Ombitasvir), ABT-333 (Dasabuvir) and ABT-450/Ritonavir (combination was called Viekira Pak);